Much information concerning the serotonin 5-HT1A receptor subtype has been generated since its discovery in 1981 (Pedigo et al., J. Neurochem. 1981, 36, 220) and subsequent cloning in 1988 (Fargin et al., Nature 1988, 335, 358). Numerous preclinical studies suggest the potential usefulness of 5-HT1A antagonists in the treatment of various diseases and disorders of the central nervous system (CNS), particularly anxiety and depression. Preclinical and clinical data now indicate that compounds that antagonize 5-HT1A receptors may find use in the treatment, prevention and amelioration of central nervous system diseases and disorders, including anxiety, depression, schizophrenia and cognitive deficits resulting from neurodegenerative disorders like Alzheimer's disease; the enhancement of antidepressant activity; the treatment and amelioration of prostate cancer; and the treatment for smoking cessation and nicotine withdrawal. K. Rasmussen and V. P. Rocco, “Recent Progress in Serotonin (5-HT)1A Receptor Modulators,” Annual Reports in Medicinal Chemistry, Volume 30, J. A. Bristol, ed., 1–9 (1995); L. E. Schechter and M. G. Kelly, “An Overview of 5-HT1A Receptor Antagonists: Historical Perspective and Therapeutic Targets,” Current Drugs Serotonin ID Research Alert 1997, 2, 299–309.
Because antagonists of 5-HT1A receptors are expected to be useful in the treatment, prevention and amelioration of central nervous system diseases, the enhancement of antidepressant activity, the treatment and amelioration of prostate cancer, and the treatment for smoking cessation and nicotine withdrawal, it would be desirable to develop new compounds that are capable of binding to 5-HT1A receptors and antagonizing their activity. The novel bicyclic indolyl derivatives of this invention are serotonergic agents that antagonize 5-HT1A receptors and thus are expected to be beneficial in these and other important uses.